Peptide fragments of the CD4 antigen were synthesized and tested for anti-viral activity. A derivatized 19 amino acid fragment of the molecule inhibits HIV-mediated T-lymphocyte fusion and HTLV-IIIB infection of CEM cells, with an ED50 of 10-100 muM in the presence of approximately 250TCID50 of the virus. The peptide is ineffective to block T-cell infection by HTLV-I, or to block other CD4-dependent cellular responses, e.g. the mixed lymphocyte reaction.